Local Ca²⁺ signaling and EC coupling in heart: Ca²⁺ sparks and the regulation of the [Ca²⁺]_i transient

The elementary event of Ca²⁺ release in hearts is the Ca²⁺ spark. It occurs at a low rate during diastole, activated only by the low cytosolic [Ca²⁺]_i. Synchronized activation of many sparks is due to the high local [Ca²⁺]_i in the region surrounding the sarcoplasmic reticulum (SR) Ca²⁺ release channels and is responsible for the systolic [Ca²⁺]_i transient. The biophysical basis of this calcium signaling is discussed. Attention is placed on the local organization of the ryanodine receptors (SR Ca²⁺ release channels, RyRs) and the other proteins that underlie and modulate excitation-contraction (EC) coupling. A brief review of specific elements that regulate SR Ca²⁺ release (including SR lumenal Ca²⁺ and coupled gating of RyRs) is presented. Finally integrative calcium signaling in heart is presented in the context of normal heart function and heart failure.